Glomerulonephritis

Acute Post-Streptococcal Glomerulonephritis
Nephrotic Syndrome

Acute Post-Streptococcal Glomerulonephritis
-Post-infection with Group A Streptococcus
-Route respiratory; Skin injury
-Most common in school-age children
-Rare in infant

Pathophysiology
-Development of IgG 2-3 weeks after infection
-Antigen-antibody complex formation
-Deposited on glomerular capillary wall
-Activation of complement system
-Proliferation of mesangial and epithelial cells
-Infiltration of polymorphonuclear leukocytes in mesangium
-Renal biopsy–>Immunofluorescence–>IgG and C3 deposits

Clinical Features
-Ranging from asymptomatic –> heart failure; hypertensive encephalopathy
-Presentations: Malaise, anorexia, oligouria, smoky/brownish urine, facial puffiness, ankle oedema.
-May: Hypertension: Headache, vomiting, visual disturbance. Cardiac failure: cough, dyspnoea, chest pain, tachycardia, frothy bloo-stained sputum. Loin pain.
-Elevation of serum urea and creatinine

Management
+Bed Rest
+Antibiotics – 10 days penicillin
+Diet – salt restriction, protein restriction (1g/kg/day)
+Severe hypertension/encephalopathy
-diastolic P > 100mmHg
-antihypertensives: nefedipine, hydralazine, diazoxide
+Acute renal failure
-usually resolves within 2-3 weeks
-intravenous frusemide (severe oliguria, electrolyte and acid-base imbalance)
+Acute cardiac failure (left ventricule) – rare

Nephrotic Syndrome
-Clinical syndrome with gross proteinuria –> hypoalbuminaemia, oedema, ascites. Hyperlipidaemia usually present.
-Primary and Secondary causes:

Primary:
*Minimal change lesion
*Focal Segmental Glomerulosclerosis
*Mesangial Proliferative Glomerulonephritis
*Membrano-Proliferative Glomerulonephritis
*Membraneous Glomerulonephritis
*Congenital Nephrotic Syndrome

Secondary:
*Infection: Syphilis, Toxoplasmosis, Hep B, Post-streptococcal Glomerulonephritis, bacterila endocarditis, Quartan malaria.
*Drugs: Penicillamine, troxidone, heavy metals.
*Systemic diseases: Henoch-Schonlein purpura, SLE, long-standing DM.
*Malignancies: Hodgkin’s disease, leukaemia, lymphosarcoma.
*Others: CCF, Renal vein obstruction.

Minimal Change Lesion
-Commonest
-Male preponderance
-Mainly < 6years
-80% of nephrotic syndrome < 15 years of age

Pathophysiology
-T-cell abnormalities
-Production of lymphokine
-Increases permeability of basement membrane
-Normal Light Microscopy & Immunofluorescence
-Swelling + Fusion of foot processes of epithelial cells on Electron microscopy

Pathogenesis of oedema in Nephrotic Syndrome

Clinical Features
-Gradual onset
-Facial puffiness, ankle oedema, abdominal distension –> whole body swelling.
-Oedema in morning –> subsides in evening
-Urine clear & frothy
-Albuminuria +++ to ++++
-Usually BP normal, no hematuria
-Serum Albumin < 25g/L
-Elevated serum Cholesterol
-Nomal serum urea & creatinine
-GFR normal
-Minor: Hypertension, microscopic hematuria, reduced GFR (hypovolaemia)

Management
+Bed rest – severe gross oedema
+2mg/kg/day prednisolone –> remission + 2-4 weeeks continuation – 2/3 divided doses
+Remission is ‘complete loss of proteinuria, serum Albumin > 24g/L
+Then 1.5mg/kg/day single morning dose / 2mg/kg/day alternate day for 4 weeks
+Cyclophosphamide 3mg/kg/day single morning dose (if dev side effect to steroid)

Complications
1. Infections
-peritonitis, pneumonia, cellulitis & septicaemia
-give broad spectrum antibiotic
2. Severe hypovolaemia
-suspected if grossly oedematous, abdominal pain, vomiting, rapid pulses, cold extremities.
-serum Albumin < 12g/L
3. Respiratory embarrassment
-due to pleural effusion, severe ascites
4. Hypercoagulable state
-due to haemoconcentration , loss of blood factors –> give aspirin

Refer Table for differences between Minimal Change NS & Significant Glomerular Lesions NS

Focal Segmental Glomerulosclerosis (FSGS)
-5-10% of NS
-Same clinical Presentation as Minimal Change NS
-10-15% response to steroid initially, later become steroid resistant
-May present with hypertension, haematuria, casts.
-Biopsy: Focal areas of segmental sclerosis.
-Immunofluorescence: Hyalinosis with IgM & IgG.
-Later develop chronic renal failure –> end stage renal disease in 10 years.

Membrano-proliferative Glomerulonephritis
-8% of NS
-Usually gross haematuria.
-May present as Acute nephritis.

Mesangial Proliferative Glomerulonephritis
-Usually resistant to steroid. Can have partial response.
-Frequent episodes of heavy proteinuria with severe oedema.

Membranous Glomerulonephritis
-Rare.
-Can present as asymtomatic proteinuria.
-Some response to steroid, but rarely remit completely.
-Associated with Syphylis, Toxoplasmosis, Hepatitis B, Malignancies.

Congenital NS
-1st few month of life.
-Causes:
-Intrauterine infection: Syphylis, Toxoplasmosis.
-Renal vein thrombosis.
-Finnish type Congenital NS:
-High level of alpha-fetoprotein in amniotic fluid.
-100% mortality without renal transplant.